Summary This proposal requests R13 support for the second meeting of the Gordon Research Conference (GRC) on Modulation of Neural Circuits & Behavior: Origins and Diversity of Neuromodulatory Mechanisms that Serve Basic Biological Needs, to be held on June 4-9, 2017, in Newry, Maine. Understanding how the human brain works will require more than the mapping of neural connectivities, because the information processing at each neuronal connection will depend on the interplay among many external and internal factors. Such modulatory mechanisms can drastically enhance or dampen distinct types of neural processes and animal behaviors in response to different environmental cues. Not surprisingly, modulators have been implicated in many neurological disorders that range from learning disabilities, addiction and depression to the cognitive decline associated with aging-related diseases. Thus, neuromodulation is necessary to promote neuronal homeostasis and optimize the individuals' survival in changing environments, which would drive the evolution of neural circuit diversity. The successful first GRC meeting on neuromodulation in Hong Kong, in 2015, brought together scientists from the US and non-US countries. The second meeting in Maine in 2017 will continue to provide a much-needed forum to better achieve the integration of concepts highlighted in different vertebrate and invertebrate systems studied by scientists on different continents. Thus, this forum will provide a global perspective of the diversity and conserved common principles in evolution for the role of neuromodulation in physiological processes and behavioral expression. This second meeting will focus on the origin and evolution of neuromodulation in serving basic biological needs, such as food, sleep, sex, and complex social behaviors, since mechanistic insights into its origins and evolution should allow us to understand how neuromodulation can arise in different contexts and promote healthy brain function. This meeting is unique, since it brings together scientists from disparate fields to foster collaborative ideas and activities in the synthesis of the common principles of neuromodulation. This will be facilitated by specific sections of the program devoted to general discussions that will cover the presentations that address the common themes of each day. More importantly, our second meeting will have an overall general discussion during the closing session, which will integrate all the diverse findings presented at the meeting, thus further advancing our understanding of neuromodulation and its importance in healthy brain function. Finally, this meeting will feature participants of different generations, with a proper representation of early pioneering investigators, current leaders and junior investigators, providing an opportunity for intimate exchanges of knowledge and ideas. Together these should drive promising future directions in the study of neuromodulation, which should be in line with the mission of NINDS and its sister institutes, NIDA, NICHD, NIA and NIDCD.